Hydrogel tablet for intestinal administration and application

Abstract

The invention discloses a hydrogel tablet for intestinal administration and application, the hydrogel tablet comprises a tablet coating and a hydrogel tablet core, the materials for preparing the tablet coating comprise starch and dextrin, the hydrogel tablet core comprises polyvinyl alcohol, 2-hydroxyethyl methacrylate and a medicine, and the hydrogel tablet core is prepared from polyvinyl alcohol, 2-hydroxyethyl methacrylate and the medicine. The medicine is usually at least one of lutein, vitamins, carotene and probiotics. The hydrogel tablet which is used for intestinal administration and can load the medicine shows excellent water absorption performance, high medicine loading capacity and stable chemical properties. When the hydrogel is applied to intestinal administration treatment, the characteristics of the hydrogel are fully exerted, specifically, the hydrogel takes effect quickly, the medicinal duration is long, the hydrogel can effectively promote space approaching of a drug and a cross-linking agent, drug release is adjusted or drug activity is prevented from being influenced by a severe intestinal environment, and the intestinal residence time of a drug library is prolonged.

Description

Technical Field

[0001] The invention belongs to the field of biomedical materials, and particularly relates to a hydrogel tablet for intestinal administration and its application. Background Art

[0002] With the development of modern medicine, the research of drug delivery systems has gradually become an important field of drug development. Traditional drug delivery methods often face problems such as low bioavailability of drugs in the body, uneven release rate, and side effects. Therefore, developing new drug delivery systems to improve the efficacy and safety of drugs has become the focus of research.

[0003] As an emerging drug delivery method, the enteral drug delivery system has attracted widespread attention because it can achieve targeted drug release through the oral route. The particularity of the intestinal environment makes the absorption efficiency of drugs in the small intestine relatively high, especially for those drugs that are easily destroyed by gastric acid. The enteral drug delivery system can effectively protect the drugs and ensure that they still have good activity when they reach the target site.

[0004] However, the application of drugs in intestinal drug delivery therapy faces difficulties such as poor solubility, low bioavailability and poor stability. They are sensitive to low pH and enzymatic action in the gastrointestinal tract, have poor chemical stability, and their isoprenoid structure makes them prone to accumulation in the intestinal mucosa, further affecting the therapeutic effect. Although nanotechnology can improve the dispersibility of drugs, external mechanical forces and extreme environments can easily destroy the nanostructure, making the release difficult to control. Summary of the invention

[0005] In order to solve the above technical problems, the present invention provides a hydrogel tablet for intestinal administration and its application.

[0006] Hydrogel is a polymer with a three-dimensional network structure that can absorb water and swell to form a gel state. Its unique physical and chemical properties enable hydrogel to exhibit different behaviors under different environmental conditions (such as pH value, temperature, etc.), thereby achieving precise control of drug release.

[0007] In one aspect, the present invention provides a hydrogel tablet for intestinal administration, the hydrogel tablet comprising a tablet coating and a hydrogel core, wherein the material for making the tablet coating comprises starch and dextrin, and the hydrogel core comprises polyvinyl alcohol, 2-hydroxyethyl methacrylate and a drug.

[0008] Furthermore, the hydrogel core comprises 10 to 20 parts of polyvinyl alcohol, 2 to 5 parts of 2-hydroxyethyl methacrylate and 10 to 25 parts of drugs by weight.

[0009] Furthermore, the tablet coating comprises 10 to 20 parts of starch and 10 to 20 parts of dextrin by weight.

[0010] Furthermore, the hydrogel tablet comprises, by weight, 10 to 20 parts of polyvinyl alcohol, 2 to 5 parts of 2-hydroxyethyl methacrylate, 10 to 20 parts of tablet coating and 10 to 25 parts of drugs.

[0011] In some specific embodiments, the hydrogel core further includes a crosslinking agent, and the hydrogel core includes 10 to 20 parts of polyvinyl alcohol, 2 to 5 parts of 2-hydroxyethyl methacrylate, 3 to 5 parts of the crosslinking agent, and 10 to 25 parts of the drug by weight.

[0012] Furthermore, the cross-linking agent is N,N'-methylenebisacrylamide and potassium persulfate.

[0013] As a preferred embodiment, the drug in the hydrogel tablet acts on the intestine.

[0014] Furthermore, the drug is at least one of lutein, vitamins, carotene, and probiotics.

[0015] The preparation process of the hydrogel core of the present invention comprises mixing the polyvinyl alcohol, 2-hydroxyethyl methacrylate and the drug according to a weight ratio, heating and stirring until the mixed solution is uniform, and dehydrating and pressing to obtain the hydrogel core.

[0016] On the other hand, the present invention also provides the use of the hydrogel tablet in intestinal administration.

[0017] The drug-loaded hydrogel tablets for intestinal administration of the present invention exhibit excellent water absorption performance, high drug loading and stable chemical properties. When the hydrogel is applied to intestinal drug administration treatment, its characteristics are fully utilized, specifically manifested in rapid onset, long duration of medicinal use, and can effectively promote the spatial proximity of drugs and cross-linking agents, regulate drug release or protect drug activity from the influence of harsh intestinal environment, and increase the intestinal residence time of the drug library. The materials used in the present invention have a wide range of sources, relatively low cost, and the preparation method is simple and easy, and it is very easy to achieve large-scale industrial production. DETAILED DESCRIPTION

[0018] In order to enable those skilled in the art to better understand the present application, the technical solutions in the embodiments of the present application are described clearly and completely below. Obviously, the described embodiments are only part of the embodiments of the present application, not all of the embodiments. Based on the embodiments in the present application, all other embodiments obtained by ordinary technicians in the field without creative work should fall within the scope of protection of the present application.

[0019] It should be noted that the terms "include" and "have" and any variations thereof are intended to cover non-exclusive inclusions. For example, a process, method, system, product or apparatus comprising a series of steps or units is not necessarily limited to those steps or units explicitly listed, but may include other steps or units not explicitly listed or inherent to these processes, methods, products or apparatus.

[0020] In recent years, the delivery method of nanoparticles combined with hydrogels has attracted attention. Hydrogels have a three-dimensional network structure that can stably encapsulate lipophilic substances and achieve sustained release, thereby improving targeted delivery efficiency and therapeutic effects. In addition, sticky polymers can prolong the residence time of active ingredients in the intestine, further enhancing the anti-inflammatory effect.

[0021] 2-Hydroxyethyl methacrylate (HEMA) and polyvinyl alcohol (PVA) are two commonly used hydrogel materials. HEMA is a synthetic polymer with good biocompatibility, degradability and mechanical strength, which can effectively carry drugs and control their release rate. PVA is extracted from natural polysaccharides, has good gelation properties and biodegradability, and can form stable hydrogels in neutral or weakly alkaline environments. The combination of these two materials forms a responsive hydrogel system that can optimize the drug release process in the intestinal environment. In intestinal drug delivery, the degradation rate and drug release characteristics of the hydrogel are key factors. By adjusting the degree of polymerization of HEMA and the concentration of PVA, the degradation rate and drug release rate of the hydrogel can be precisely controlled. This adjustability enables the hydrogel to achieve delayed release in the gastrointestinal tract, reduce the effect of gastric acid on the drug, and provide sustained and controlled drug release in the small intestine and its posterior segments, thereby improving the bioavailability of the drug.

[0022] In addition, the preparation process of hydrogel tablets is also crucial. By dissolving HEMA and PVA in an appropriate solvent, and then mixing and drying, a stable hydrogel sheet can be prepared. This hydrogel tablet can not only effectively load drugs, but also achieve targeted release under specific conditions, and is particularly suitable for drugs that require slow release, such as anticancer drugs and anti-inflammatory drugs. In the field of drug delivery, 2-hydroxyethyl methacrylate-polyvinyl alcohol hydrogel tablets show broad application prospects. By controlling the release of drugs in the gastrointestinal tract, the stability and bioavailability of drugs can be effectively improved, especially for drugs that are easily destroyed by gastric acid. In addition, the system can also achieve targeted release of drugs, improve therapeutic effects and reduce side effects. In summary, 2-hydroxyethyl methacrylate-polyvinyl alcohol hydrogel tablets, as a new intestinal drug delivery system, are expected to play an important role in future drug treatments with their excellent biocompatibility, adjustable release characteristics and good drug loading capacity, providing patients with safer and more effective treatment options.

[0023] This embodiment provides a hydrogel tablet for intestinal administration, including a tablet coating and a hydrogel core, wherein the material for making the tablet coating includes starch and dextrin, and the hydrogel core includes polyvinyl alcohol, 2-hydroxyethyl methacrylate and a drug. After the coating containing starch and dextrin contacts the digestive fluid in the body, it disperses and dissolves, causing the internal hydrogel core to gel. Administration method: oral.

[0024] As a preferred embodiment, the tablet coating includes 10 to 20 parts of starch and 10 to 20 parts of dextrin by weight.

[0025] The hydrogel core comprises 10-20 parts of polyvinyl alcohol, 2-5 parts of 2-hydroxyethyl methacrylate and 10-25 parts of drugs by weight.

[0026] Specifically, the hydrogel tablet comprises, by weight, 10 to 20 parts of polyvinyl alcohol, 2 to 5 parts of 2-hydroxyethyl methacrylate, 10 to 20 parts of tablet coating and 10 to 25 parts of drugs.

[0027] In this embodiment, the drug in the hydrogel tablet acts on the intestine and can be at least one of lutein, vitamins, carotene, and probiotics, but is not limited to the above drugs. Any drug that acts on the intestine can be used in the technical solution of this embodiment.

[0028] In some specific embodiments, the hydrogel core further includes a crosslinking agent. Specifically, the hydrogel core includes 10 to 20 parts of polyvinyl alcohol, 2 to 5 parts of 2-hydroxyethyl methacrylate, 3 to 5 parts of a crosslinking agent, and 10 to 25 parts of a drug by weight.

[0029] The cross-linking agent is optional, and is N,N'-methylenebisacrylamide and potassium persulfate.

[0030] The preparation process of the hydrogel core includes mixing polyvinyl alcohol, 2-hydroxyethyl methacrylate and the drug according to a weight ratio, heating and stirring until the mixed solution is uniform, dehydrating and pressing to obtain the hydrogel core. Then, the hydrogel core is coated in a tablet coating.

[0031] Example 1

[0032] This embodiment provides a hydrogel tablet for intestinal administration, including a tablet coating and a hydrogel core, wherein the material for making the tablet coating includes starch and dextrin, and the hydrogel core includes polyvinyl alcohol, 2-hydroxyethyl methacrylate and a drug. After the coating containing starch and dextrin contacts the digestive fluid in the body, it disperses and dissolves, causing the internal hydrogel core to gel. Administration method: oral.

[0033] In this embodiment, the hydrogel tablet may optionally include 10 parts of polyvinyl alcohol, 2 parts of 2-hydroxyethyl methacrylate, 10 parts of tablet coating and 10 parts of probiotics by weight, wherein the tablet coating is made of starch and dextrin, and in this embodiment, includes 10 parts of starch and 10 parts of dextrin by weight.

[0034] Preferably, the core of the hydrogel tablet of this embodiment also includes cross-linking agents N,N'-methylenebisacrylamide and potassium persulfate. The hydrogel tablet includes 10 parts of polyvinyl alcohol, 3 parts of 2-hydroxyethyl methacrylate, 10 parts of tablet coating, 10 parts of probiotics, and 3 parts of N,N'-methylenebisacrylamide and potassium persulfate by weight.

[0035] It has been proven that hydrogel tablets containing cross-linking agents have better drug release effects than those without cross-linking agents.

[0036] Example 2

[0037] This embodiment provides a hydrogel tablet for intestinal administration, including a tablet coating and a hydrogel core, wherein the material for making the tablet coating includes starch and dextrin, and the hydrogel core includes polyvinyl alcohol, 2-hydroxyethyl methacrylate and a drug. After the coating containing starch and dextrin contacts the digestive fluid in the body, it disperses and dissolves, causing the internal hydrogel core to gel. Administration method: oral.

[0038] In this embodiment, the hydrogel tablet may optionally include 20 parts of polyvinyl alcohol, 5 parts of 2-hydroxyethyl methacrylate, 20 parts of tablet coating and 25 parts of carotene by weight, wherein the tablet coating is made of starch and dextrin, and in this embodiment includes 20 parts of starch and 20 parts of dextrin by weight.

[0039] Preferably, the core of the hydrogel tablet of this embodiment also includes cross-linking agents N,N'-methylenebisacrylamide and potassium persulfate. The hydrogel tablet includes 20 parts of polyvinyl alcohol, 5 parts of 2-hydroxyethyl methacrylate, 20 parts of tablet coating, 25 parts of carotene, and 5 parts of N,N'-methylenebisacrylamide and potassium persulfate by weight.

[0040] It has been proven that hydrogel tablets containing cross-linking agents have better drug release effects than those without cross-linking agents.

[0041] Example 3

[0042] This embodiment provides a hydrogel tablet for intestinal administration, including a tablet coating and a hydrogel core, wherein the material for making the tablet coating includes starch and dextrin, and the hydrogel core includes polyvinyl alcohol, 2-hydroxyethyl methacrylate and a drug. After the coating containing starch and dextrin contacts the digestive fluid in the body, it disperses and dissolves, causing the internal hydrogel core to gel. Administration method: oral.

[0043] In this embodiment, the hydrogel tablet may optionally include 15 parts of polyvinyl alcohol, 3 parts of 2-hydroxyethyl methacrylate, 15 parts of tablet coating and 15 parts of lutein by weight, wherein the tablet coating is made of starch and dextrin, and in this embodiment, includes 15 parts of starch and 15 parts of dextrin by weight.

[0044] Preferably, the core of the hydrogel tablet of this embodiment also includes cross-linking agents N,N'-methylenebisacrylamide and potassium persulfate. The hydrogel tablet includes 15 parts of polyvinyl alcohol, 3 parts of 2-hydroxyethyl methacrylate, 15 parts of tablet coating, 15 parts of lutein, and 4 parts of N,N'-methylenebisacrylamide and potassium persulfate by weight.

[0045] It has been proven that hydrogel tablets containing cross-linking agents have better drug release effects than those without cross-linking agents.

[0046] Experimental Example 1 Intestinal drug sustained release animal model experiment 1. Experimental animals: 60 male Sprague Dawley rats weighing 150-180 g were selected.

[0047] 2. Experimental materials: Hydrogel tablets for intestinal administration were prepared from the following raw materials according to the method described in the instructions: 10 parts of polyvinyl alcohol, 2 parts of 2-hydroxyethyl methacrylate, 10 parts of lutein, 3 parts of N,N'-methylenebisacrylamide and potassium persulfate, 10 parts of starch and 10 parts of dextrin.

[0048] 3. Experimental groups: 60 rats were randomly divided into 4 experimental groups, namely blank group (n=15), no cross-linking agent group (n=15), hydrogel low loading group (n=15), and hydrogel high loading group (n=15).

[0049] 4. Experimental Results

[0050] The results show that the compositions provided by the present invention all have the effect of sustained drug release and the high-dose group has the best effect.

[0051] Experimental Example 2: Intestinal drug sustained release animal model experiment 1. Experimental animals: 60 Sprague Dawley male rats weighing 150-180 g were selected.

[0052] 2. Experimental materials: Hydrogel tablets for intestinal administration were prepared from the following raw materials according to the method described in the instructions: 12 parts of polyvinyl alcohol, 3 parts of 2-hydroxyethyl methacrylate, 10 parts of vitamin B12, 3 parts of N,N'-methylenebisacrylamide and potassium persulfate, 10 parts of starch and 10 parts of dextrin.

[0053] 3. Experimental groups: 60 rats were randomly divided into 4 experimental groups, namely blank group (n=15), no cross-linking agent group (n=15), hydrogel low loading group (n=15), and hydrogel high loading group (n=15).

[0054] 4. Experimental Results

[0055] The results show that the compositions provided by the present invention have the effect of sustained drug release and the high-dose group has the best effect. The present invention also provides application of the drug-loaded hydrogel tablet in intestinal administration.

[0056] The above description is only the preferred embodiment of the present application and is not intended to limit the present application. For those skilled in the art, the present application may have various modifications and variations. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present application shall be included in the protection scope of the present application.

Claims

1. A hydrogel tablet for intestinal administration, characterized in that: The hydrogel tablet comprises a tablet coating and a hydrogel core, wherein the material for making the tablet coating comprises starch and dextrin, and the hydrogel core comprises polyvinyl alcohol, 2-hydroxyethyl methacrylate and a drug, wherein the drug is at least one of lutein, vitamins, carotene and probiotics.

2. The hydrogel tablet for enteral administration according to claim 1, characterized in that: The hydrogel core comprises 10 to 20 parts of polyvinyl alcohol, 2 to 5 parts of 2-hydroxyethyl methacrylate and 10 to 25 parts of a drug by weight.

3. The hydrogel tablet for enteral administration according to claim 2, characterized in that: The tablet coating comprises 10 to 20 parts of starch and 10 to 20 parts of dextrin by weight.

4. The hydrogel tablet for enteral administration according to claim 1, characterized in that: The hydrogel tablet comprises, by weight, 10 to 20 parts of polyvinyl alcohol, 2 to 5 parts of 2-hydroxyethyl methacrylate, 10 to 20 parts of tablet coating and 10 to 25 parts of medicine.

5. The hydrogel tablet for enteral administration according to claim 2, characterized in that: The hydrogel core also includes a crosslinking agent. The hydrogel core includes 10 to 20 parts of polyvinyl alcohol, 2 to 5 parts of 2-hydroxyethyl methacrylate, 3 to 5 parts of the crosslinking agent and 10 to 25 parts of the drug by weight.

6. The hydrogel tablet for enteral administration according to claim 5, characterized in that: The cross-linking agent is N,N'-methylenebisacrylamide and potassium persulfate.

7. The hydrogel tablet for enteral administration according to claim 1, characterized in that: The medicine in the hydrogel tablet acts on the intestine.

8. The hydrogel tablet for enteral administration according to claim 1, characterized in that: The preparation process of the hydrogel core comprises the following steps: mixing the polyvinyl alcohol, 2-hydroxyethyl methacrylate and the drug in proportion by weight, heating and stirring until the mixed solution is uniform, and dehydrating and pressing to obtain the hydrogel core.

9. Use of the hydrogel tablet according to any one of claims 1 to 7 in enteral administration.

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